PT  - JOURNAL ARTICLE
AU  - Tong Ren
AU  - Ang Ma
AU  - Rengong Zhuo
AU  - Huaying Zhang
AU  - Lu Peng
AU  - Xin Jin
AU  - Enhui Yao
AU  - Lichao Yang
TI  - Oleoylethanolamide Increases Glycogen Synthesis and Inhibits Hepatic Gluconeogenesis via the LKB1/AMPK Pathway in Type 2 Diabetic Model
AID  - 10.1124/jpet.119.262675
DP  - 2020 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 81--91
VI  - 373
IP  - 1
4099  - http://jpet.aspetjournals.org/content/373/1/81.short
4100  - http://jpet.aspetjournals.org/content/373/1/81.full
SO  - J Pharmacol Exp Ther2020 Apr 01; 373
AB  - Oleoylethanolamide (OEA) is an endogenous peroxisome proliferator-activated receptor α (PPARα) agonist that acts on the peripheral control of energy metabolism. However, its therapeutic potential and related mechanisms in hepatic glucose metabolism under type 2 diabetes mellitus (T2DM) are not clear. Here, OEA treatment markedly improved glucose homeostasis in a PPARα-independent manner. OEA efficiently promoted glycogen synthesis and suppressed gluconeogenesis in mouse primary hepatocytes and liver tissue. OEA enhanced hepatic glycogen synthesis and inhibited gluconeogenesis via liver kinase B1 (LKB1)/5′ AMP-activated protein kinase (AMPK) signaling pathways. PPARα was not involved in the roles of OEA in the LKB1/AMPK pathways. We found that OEA exerts its antidiabetic effect by increasing glycogenesis and decreasing gluconeogenesis via the LKB1/AMPK pathway. The ability of OEA to control hepatic LKB1/AMPK pathways may serve as a novel therapeutic approach for the treatment of T2DM.SIGNIFICANCE STATEMENT Oleoylethanolamide (OEA) exerted a potent antihyperglycemic effect in a peroxisome proliferator-activated receptor α–independent manner. OEA played an antihyperglycemic role primarily via regulation of hepatic glycogen synthesis and gluconeogenesis. The main molecular mechanism of OEA in regulating liver glycometabolism is activating the liver kinase B1/5′ AMP-activated protein kinase signaling pathways.